Analysis of 1 year virtual histology changes in coronary plaque located behind the struts of the everolimus eluting bioresorbable vascular scaffold

Serial intravascular ultrasound virtual histology (IVUS-VH) after implantation of metallic stents has been unable to show any changes in the composition of the scaffolded plaque overtime. The everolimus-eluting ABSORB scaffold potentially allows for the formation of new fibrotic tissue on the scaffolded coronary plaque during bioresorption. We examined the 12 month IVUS-VH changes in composition of the plaque behind the struts (PBS) following the implantation of the ABSORB scaffold. Using IVUS-VH and dedicated software, the composition of the PBS was analyzed in all patients from the ABSORB Cohort B2 trial, who were imaged with a commercially available IVUS-VH console (s5i system, Volcano Corporation, Rancho Cordova, CA, USA), immediately post-ABSORB implantation and at 12 month follow-up. Paired IVUS-VH data, recorded with s5i system, were available in 17 patients (18 lesions). The analysis demonstrated an increase in mean PBS area (2.39 ± 1.85 mm(2) vs. 2.76 ± 1.79 mm(2), P = 0.078) and a reduction in the mean lumen area (6.37 ± 0.90 mm(2) vs. 5.98 ± 0.97 mm(2), P = 0.006). Conversely, a significant decrease of 16 and 30% in necrotic core (NC) and dense calcium (DC) content, respectively, were evident (median % NC from 43.24 to 36.06%, P = 0.016; median % DC from 20.28 to 11.36%, P = 0.002). Serial IVUS-VH analyses of plaque located behind the ABSORB struts at 12-month demonstrated an increase in plaque area with a decrease in its NC and DC content. Larger studies are required to investigate the clinical impact of these findings.

Delayed coverage in malapposed and side-branch struts with respect to well-apposed struts in drug-eluting stents: in vivo assessment with optical coherence tomography

Background—Pathology studies on fatal cases of very late stent thrombosis have described incomplete neointimal coverage as common substrate, in some cases appearing at side-branch struts. Intravascular ultrasound studies have described the association between incomplete stent apposition (ISA) and stent thrombosis, but the mechanism explaining this association remains unclear. Whether the neointimal coverage of nonapposed side-branch and ISA struts is delayed with respect to well-apposed struts is unknown. Methods and Results—Optical coherence tomography studies from 178 stents implanted in 99 patients from 2 randomized trials were analyzed at 9 to 13 months of follow-up. The sample included 38 sirolimus-eluting, 33 biolimus-eluting, 57 everolimus-eluting, and 50 zotarolimus-eluting stents. Optical coherence tomography coverage of nonapposed side-branch and ISA struts was compared with well-apposed struts of the same stent by statistical pooled analysis with a random-effects model. A total of 34 120 struts were analyzed. The risk ratio of delayed coverage was 9.00 (95% confidence interval, 6.58 to 12.32) for nonapposed side-branch versus well-apposed struts, 9.10 (95% confidence interval, 7.34 to 11.28) for ISA versus well-apposed struts, and 1.73 (95% confidence interval, 1.34 to 2.23) for ISA versus nonapposed side-branch struts. Heterogeneity of the effect was observed in the comparison of ISA versus well-apposed struts (H=1.27; I2=38.40) but not in the other comparisons. Conclusions—Coverage of ISA and nonapposed side-branch struts is delayed with respect to well-apposed struts in drug-eluting stents, as assessed by optical coherence tomography.

Comparison between the first and second generation bioresorbable vascular scaffolds: a six month virtual histology study

To compare the intravascular ultrasound virtual histology (IVUS-VH) appearance of the polymeric struts of the first (Revision 1.0) and the second (Revision 1.1) generation bioresorbable vascular scaffold (BVS).

Deviation from Murray's law is associated with a higher degree of calcification in coronary bifurcations

Murray's law describes the optimal branching anatomy of vascular bifurcations. If Murray's law is obeyed, shear stress is constant over the bifurcation. Associations between Murray's law and intravascular ultrasound (IVUS) assessed plaque composition near coronary bifurcations have not been investigated previously.

Impact of incomplete stent apposition on long-term clinical outcome after drug-eluting stent implantation

Late acquired incomplete stent apposition (ISA) is more common after drug-eluting stent (DES) than bare metal stent (BMS) implantation and has been associated with vascular hypersensitivity and stent thrombosis (ST). We investigated the impact of incidentally discovered ISA as assessed by intravascular ultrasound (IVUS) 8 months after DES implantation on the long-term clinical outcome.

Accuracy of in vivo coronary plaque morphology assessment: a validation study of in vivo virtual histology compared with in vitro histopathology

OBJECTIVES: The goal of the present study was to compare the accuracy of in vivo tissue characterization obtained by intravascular ultrasound (IVUS) radiofrequency (RF) data analysis, known as Virtual Histology (VH), to the in vitro histopathology of coronary atherosclerotic plaques obtained by directional coronary atherectomy. BACKGROUND: Vulnerable plaque leading to acute coronary syndrome (ACS) has been associated with specific plaque composition, and its characterization is an important clinical focus. METHODS: Virtual histology IVUS images were performed before and after a single debulking cut using directional coronary atherectomy. Debulking region of in vivo histology image was predicted by comparing pre- and post-debulking VH images. Analysis of VH images with the corresponding tissue cross section was performed. RESULTS: Fifteen stable angina pectoris (AP) and 15 ACS patients were enrolled. The results of IVUS RF data analysis correlated well with histopathologic examination (predictive accuracy from all patients data: 87.1% for fibrous, 87.1% for fibro-fatty, 88.3% for necrotic core, and 96.5% for dense calcium regions, respectively). In addition, the frequency of necrotic core was significantly higher in the ACS group than in the stable AP group (in vitro histopathology: 22.6% vs. 12.6%, p = 0.02; in vivo virtual histology: 24.5% vs. 10.4%, p = 0.002). CONCLUSIONS: Correlation of in vivo IVUS RF data analysis with histopathology shows a high accuracy. In vivo IVUS RF data analysis is a useful modality for the classification of different types of coronary components, and may play an important role in the detection of vulnerable plaque.

Incomplete stent apposition and very late stent thrombosis after drug-eluting stent implantation

BACKGROUND: Stent thrombosis may occur late after drug-eluting stent (DES) implantation, and its cause remains unknown. The present study investigated differences of the stented segment between patients with and without very late stent thrombosis with the use of intravascular ultrasound. METHODS AND RESULTS: Since January 2004, patients presenting with very late stent thrombosis (> 1 year) after DES implantation underwent intravascular ultrasound. Findings in patients with very late stent thrombosis were compared with intravascular ultrasound routinely obtained 8 months after DES implantation in 144 control patients, who did not experience stent thrombosis for > or = 2 years. Very late stent thrombosis was encountered in 13 patients at a mean of 630+/-166 days after DES implantation. Compared with DES controls, patients with very late stent thrombosis had longer lesions (23.9+/-16.0 versus 13.3+/-7.9 mm; P<0.001) and stents (34.6+/-22.4 versus 18.6+/-9.5 mm; P<0.001), more stents per lesion (1.6+/-0.9 versus 1.1+/-0.4; P<0.001), and stent overlap (39% versus 8%; P<0.001). Vessel cross-sectional area was similar for the reference segment (cross-sectional area of the external elastic membrane: 18.9+/-6.9 versus 20.4+/-7.2 mm2; P=0.46) but significantly larger for the in-stent segment (28.6+/-11.9 versus 20.1+/-6.7 mm2; P=0.03) in very late stent thrombosis patients compared with DES controls. Incomplete stent apposition was more frequent (77% versus 12%; P<0.001) and maximal incomplete stent apposition area was larger (8.3+/-7.5 versus 4.0+/-3.8 mm2; P=0.03) in patients with very late stent thrombosis compared with controls. CONCLUSIONS: Incomplete stent apposition is highly prevalent in patients with very late stent thrombosis after DES implantation, suggesting a role in the pathogenesis of this adverse event.

Temporary scaffolding of coronary arteries with bioabsorbable magnesium stents: a prospective, non-randomised multicentre trial

BACKGROUND: Coronary stents improve immediate and late results of balloon angioplasty by tacking up dissections and preventing wall recoil. These goals are achieved within weeks after angioplasty, but with current technology stents permanently remain in the artery, with many limitations including the need for long-term antiplatelet treatment to avoid thrombosis. We report a prospective multicentre clinical trial of coronary implantations of absorbable magnesium stents. METHODS: We enrolled 63 patients (44 men; mean age 61.3 [SD 9.5 years]) in eight centres with single de novo lesions in a native coronary artery in a multicentre, non-randomised prospective study. Follow-up included coronary angiography and intravascular ultrasound at 4 months and clinical assessment at 6 months and 12 months. The primary endpoint was cardiac death, non-fatal myocardial infarction, or clinically driven target lesion revascularisation at 4 months FINDINGS: 71 stents, 10-15 mm in length and 3.0-3.5 mm in diameter, were successfully implanted after pre-dilatation in 63 patients. Diameter stenosis was reduced from 61.5 (SD 13.1%) to 12.6 (5.6%) with an acute gain of 1.41 mm (0.46 mm) and in-stent late loss of 1.08 mm (0.49 mm). The ischaemia-driven target lesion revascularisation rate was 23.8% after 4 months, and the overall target lesion revascularisation rate was 45% after 1 year. No myocardial infarction, subacute or late thrombosis, or death occurred. Angiography at 4 months showed an increased diameter stenosis of 48.4 (17.0%). After serial intravascular ultrasound examinations, only small remnants of the original struts were visible, well embedded into the intima. Neointimal growth and negative remodelling were the main operating mechanisms of restenosis. INTERPRETATION: This study shows that biodegradable magnesium stents can achieve an immediate angiographic result similar to the result of other metal stents and can be safely degraded after 4 months. Modifications of stent characteristics with prolonged degradation and drug elution are currently in development.

[The role of percutaneus coronary interventions in the treatment of coronary artery disease]

In industrial countries, cardiovascular diseases remain the primary cause of death. This review summarizes the role of percutaneous coronary interventions (PCI) in the treatment of coronary heart disease. Interventional therapy of coronary artery disease was initiated in 1977 with the introduction of balloon angioplasty by Andreas Grüntzig in Zurich. Technical progress since has been related to construction and materials of catheters, but also to digital processing of x-ray imaging. Additional methods - rotablation, atherectomy, laser, intravascular ultrasound, and most importantly stent implantation were developed. Only stents significantly changed the procedure. They are today an integral part of PCI.

Differences in coronary artery plaques between target and non-target vessels

We used intravascular ultrasound (IVUS) and virtual histology (VH) to assess the differences of plaque burden and composition between target coronary arteries containing the culprit lesion and non-target coronary arteries.

Dynamics of vessel wall changes following the implantation of the Absorb everolimus-eluting bioresorbable vascular scaffold: a multi-imaging modality study at 6, 12, 24 and 36 months

Aims: To assess observations with multimodality imaging of the Absorb bioresorbable everolimus-eluting vascular scaffold performed in two consecutive cohorts of patients who were serially investigated either at 6 and 24 months or at 12 and 36 months. Methods and results: In the ABSORB multicentre single-arm trial, 45 patients (cohort B1) and 56 patients (cohort B2) underwent serial invasive imaging, specifically quantitative coronary angiography (QCA), intravascular ultrasound (IVUS), radiofrequency backscattering (IVUS-VH) and optical coherence tomography (OCT). Between one and three years, late luminal loss remained unchanged (6 months: 0.19 mm, 1 year: 0.27 mm, 2 years: 0.27 mm, 3 years: 0.29 mm) and the in-segment angiographic restenosis rate for the entire cohort B (n=101) at three years was 6%. On IVUS, mean lumen, scaffold, plaque and vessel area showed enlargement up to two years. Mean lumen and scaffold area remained stable between two and three years whereas significant reduction in plaque behind the struts occurred with a trend toward adaptive restrictive remodelling of EEM. Hyperechogenicity of the vessel wall, a surrogate of the bioresorption process, decreased from 23.1% to 10.4% with a reduction of radiofrequency backscattering for dense calcium and necrotic core. At three years, the count of strut cores detected on OCT increased significantly, probably reflecting the dismantling of the scaffold; 98% of struts were covered. In the entire cohort B (n=101), the three-year major adverse cardiac event rate was 10.0% without any scaffold thrombosis. Conclusions: The current investigation demonstrated the dynamics of vessel wall changes after implantation of a bioresorbable scaffold, resulting at three years in stable luminal dimensions, a low restenosis rate and a low clinical major adverse cardiac events rate.

The edge vascular response following implantation of the Absorb everolimus-eluting bioresorbable vascular scaffold and the XIENCE V metallic everolimus-eluting stent. First serial follow-up assessment at six months and two years: insights from the first-in-man ABSORB Cohort B and SPIRIT II trials

AIMS To assess serially the edge vascular response (EVR) of a bioresorbable vascular scaffold (BVS) compared to a metallic everolimus-eluting stent (EES). METHODS AND RESULTS Non-serial evaluations of the Absorb BVS at one year have previously demonstrated proximal edge constrictive remodelling and distal edge changes in plaque composition with increase of the percent fibro-fatty (FF) tissue component. The 5 mm proximal and distal segments adjacent to the implanted devices were investigated serially with intravascular ultrasound (IVUS), post procedure, at six months and at two years, from the ABSORB Cohort B1 (n=45) and the SPIRIT II (n=113) trials. Twenty-two proximal and twenty-four distal edge segments were available for analysis in the ABSORB Cohort B1 trial. In the SPIRIT II trial, thirty-three proximal and forty-six distal edge segments were analysed. At the 5-mm proximal edge, the vessels treated with an Absorb BVS from post procedure to two years demonstrated a lumen loss (LL) of 6.68% (-17.33; 2.08) (p=0.027) with a trend toward plaque area increase of 7.55% (-4.68; 27.11) (p=0.06). At the 5-mm distal edge no major changes were evident at either time point. At the 5-mm proximal edge the vessels treated with a XIENCE V EES from post procedure to two years did not show any signs of LL, only plaque area decrease of 6.90% (-17.86; 4.23) (p=0.035). At the distal edge no major changes were evident with regard to either lumen area or vessel remodelling at the same time point. CONCLUSIONS The IVUS-based serial evaluation of the EVR up to two years following implantation of a bioresorbable everolimus-eluting scaffold shows a statistically significant proximal edge LL; however, this finding did not seem to have any clinical implications in the serial assessment. The upcoming imaging follow-up of the Absorb BVS at three years is anticipated to provide further information regarding the vessel wall behaviour at the edges.

Everolimus immunosuppression in de novo heart transplant recipients: What does the evidence tell us now?

The efficacy of everolimus with reduced cyclosporine in de novo heart transplant patients has been demonstrated convincingly in randomized studies. Moreover, everolimus-based immunosuppression in de novo heart transplant recipients has been shown in two randomized trials to reduce the increase in maximal intimal thickness based on intravascular ultrasound, indicating attenuation of cardiac allograft vasculopathy (CAV). Randomized trials of everolimus in de novo heart transplantation have also consistently shown reduced cytomegalovirus infection versus antimetabolite therapy. In maintenance heart transplantation, conversion from calcineurin inhibitors to everolimus has demonstrated a sustained improvement in renal function. In de novo patients, a renal benefit may only be achieved if there is an adequate reduction in exposure to calcineurin inhibitor therapy. Delayed introduction of everolimus may be appropriate in patients at high risk of wound healing complications, e.g. diabetic patients or patients with ventricular assist device. The current evidence base suggests that the most convincing reasons for use of everolimus from the time of heart transplantation are to slow the progression of CAV and to lower the risk of cytomegalovirus infection. A regimen of everolimus with reduced-exposure calcineurin inhibitor and steroids in de novo heart transplant patients represents a welcome addition to the therapeutic armamentarium.

Quantitative myocardial contrast echocardiography: a new method for the non-invasive detection of chronic heart transplant rejection

Chronic heart transplant rejection, i.e. cardiac allograft vasculopathy (CAV) is a major adverse prognostic factor after heart transplantation (HTx). This study tested the hypothesis that the relative myocardial blood volume (rBV) as quantified by myocardial contrast echocardiography accurately detects severe CAV as defined by coronary intravascular ultrasound (IVUS).

Natural history of optical coherence tomography-detected non-flow-limiting edge dissections following drug-eluting stent implantation

Aims: Angiographic evidence of edge dissections has been associated with a risk of early stent thrombosis. Optical coherence tomography (OCT) is a high-resolution technology detecting a greater number of edge dissections -particularly non-flow-limiting- compared to angiography. Their natural history and clinical implications remain unclear. The objectives of the present study were to assess the morphology, healing response, and clinical outcomes of OCT-detected edge dissections using serial OCT imaging at baseline and at one year following drug-eluting stent (DES) implantation. Methods and results: Edge dissections were defined as disruptions of the luminal surface in the 5 mm segments proximal and distal to the stent, and categorised as flaps, cavities, double-lumen dissections or fissures. Qualitative and quantitative OCT analyses were performed every 0.5 mm at baseline and one year, and clinical outcomes were assessed. Sixty-three lesions (57 patients) were studied with OCT at baseline and one-year follow-up. Twenty-two non-flow-limiting edge dissections in 21 lesions (20 patients) were identified by OCT; only two (9%) were angiographically visible. Flaps were found in 96% of cases. The median longitudinal dissection length was 2.9 mm (interquartile range [IQR] 1.6-4.2 mm), whereas the circumferential and axial extensions amounted to 1.2 mm (IQR: 0.9-1.7 mm) and 0.6 mm (IQR: 0.4-0.7 mm), respectively. Dissections extended into the media and adventitia in seven (33%) and four (20%) cases, respectively. Eighteen (82%) OCT-detected edge dissections were also evaluated with intravascular ultrasound which identified nine (50%) of these OCT-detected dissections. No stent thrombosis or target lesion revascularisation occurred up to one year. At follow-up, 20 (90%) edge dissections were completely healed on OCT. The two cases exhibiting persistent dissection had the longest flaps (2.81 mm and 2.42 mm) at baseline. Conclusions: OCT-detected edge dissections which are angiographically silent in the majority of cases are not associated with acute stent thrombosis or restenosis up to one-year follow-up.